Researchers used three approaches to study whether probiotics could help prevent sarcopenia (age-related loss of muscle mass, strength and physical function), analyzing human data from the United Kingdom, the United States and an international gut-microbiome database to compare probiotic use with muscle health.
They also tested probiotic-derived substances on muscle cells in the laboratory, and used computer simulations and machine learning to explore possible mechanisms and predict sarcopenia risk.
“Supplementation with probiotics may provide a significant, clinically relevant benefit to the health of older adults’ skeletal muscle and be protective against sarcopenia through synergistic anti-inflammatory, mitochondrial, and anabolic regulatory effects,” they wrote in Frontiers in Cellular and Infection Microbiology.
The gut–muscle axis
Several biological processes drive muscle loss during aging. Chronic inflammation, mitochondrial dysfunction, reduced muscle protein synthesis, anabolic resistance and metabolic problems can damage muscle and reduce its ability to repair itself.
The gut–muscle axis may play an important role in this process, as gut bacteria can influence inflammation, nutrient absorption, metabolism, and muscle function. They also produce short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate, which can support mitochondrial function, reduce inflammation, improve insulin sensitivity and influence muscle-building pathways.
Research suggests that probiotics may improve gut health and support muscle function by reducing inflammation, improving metabolism, supporting mitochondria, and promoting muscle regeneration. However, as the researchers of the new paper note, the mechanisms are not fully understood and evidence remains fragmented.
Study details
The researchers assessed NHANES data from adults aged 60 years and older, comparing regular probiotic users with non-users and assessed handgrip strength, muscle mass, protein intake, and inflammation using C-reactive protein (CRP) levels. They also assessed UK Biobank data from adults also aged 60 years and older, identifying regular probiotic consumers based on supplement and yoghurt intake and compared their handgrip strength, fat-free mass, BMI, physical activity, and inflammation with those of non-consumers.
They used Gut Microbiota Repository (GMrepo) data to examine gut microbiome data from older adults who consumed probiotics or fermented foods. They assessed microbiome diversity and the abundance of probiotic-related and SCFA-producing bacteria.
For the laboratory experiments, the researchers tested three probiotic strains: Lactobacillus rhamnosus, Lactobacillus plantarum, and Bifidobacterium longum. They collected bacterial metabolites to create probiotic-conditioned media (PCM) then treated C2C12 muscle cells with PCM or the SCFAs acetate, propionate and butyrate before comparing these cells with untreated control cells.
They also used computer simulations (molecular docking) to predict how the SCFAs might interact with proteins mTOR, AMPK, and NF-κB which are involved in muscle growth, energy use and inflammation.
Results showed consistent associations between probiotic use and better muscle health across the three datasets, with probiotic users (34.3% of the NHANES group and 30% of the UK Biobank group) showing greater muscle strength and muscle mass than non-users. In GMrepo, people with more probiotic-associated bacteria had greater gut microbiome diversity and different gut bacterial communities.
Across all three datasets, diagnosed sarcopenia was less common among probiotic users, occurring in 20% of probiotic users compared with 26% of non-users in NHANES, 20% compared with 24% in UK Biobank, and 18% compared with 26% in the GMrepo groups. Probiotic use was also associated with lower inflammation, although the strength of these effects varied by age and sex.
The convergence of results across NHANES, UK Biobank, and GMrepo data enhances external validity, the researchers wrote.
The laboratory experiment results showed that PCM helped muscle cells grow and develop, increasing the number of muscle cells that joined together to form mature muscle fibers, raising myotube fusion from 78.9% to 85.6%, and increasing muscle fiber thickness. It also increased the activity of key muscle-development genes.
“Simultaneous down-regulation of a few key inflammatory mediators (NF-κB, TNF-α) and up-regulation of PGC-1α provide evidence for its dual mechanism of action,” the researchers noted.
The molecular docking results showed that all three SCFAs could interact with proteins involved in muscle growth, energy use, and inflammation, and butyrate had the strongest predicted interaction with all three proteins.
The researchers noted that the molecular docking outcomes suggested “direct molecular engagement of the probiotic-derived metabolites with pathways involved in muscle metabolism and inflammation.”
The use of AI
The researchers also used AI to combine clinical, nutritional, inflammatory, and gut microbiome data to predict sarcopenia risk.
They trained two AI models (Random Forest and XGBoost) using 70% of the data and tested them on the remaining 30%.
The machine-learning analysis showed that combining muscle strength, protein intake, inflammation and gut microbiome data could improve sarcopenia risk prediction, which the researchers noted suggested that AI could eventually help identify people at higher risk and support personalized nutrition strategies.
“The AI framework, therefore, lays the groundwork for informed precision geriatrics, including early risk stratification, precision preventive interventions, and personalized nutritional-microbiome modulation strategies,” they concluded.
“This comprehensive framework positions probiotics as a precision nutrition intervention for sarcopenia prevention, targeting muscle-sparing effects through microbiome modulation that stimulates coordinated immunometabolic and anabolic actions, with AI-enhanced, individualized risk prediction for healthy aging.”
They noted that future research should consider longer clinical trials, more advanced laboratory and molecular studies, and further development and real-world testing of AI to support personalized probiotic and nutrition strategies for preventing sarcopenia.
Source: Frontiers in Cellular and Infection Microbiology doi: 10.1016/j.yrtph.2023.105496; “Probiotic supplementation as a nutritional strategy for the prevention and management of sarcopenia in older adults.” Authors: Wang, D. et al.
